Decreased expression or function of UCP3 could reduce energy expenditure and increase the storage of energy. The aim of our study was to investigate the influence of - 55CT polymorphism of the UCP3 gene on insulin concentrations and metabolic parameters secondary to two hypocaloric diets in obese patients. A population of 131 obese (body mass index >30), nondiabetic outpatients was analyzed in a prospective way. Before and after 2 months on two different hypocaloric diets, bipolar electrical bioimpedance, blood pressure measurement, serial assessment of nutritional intake with 3d of written food records, and biochemical analysis were performed. The statistical analysis was performed based on a dominant model. With diet type I (low fat) and diet type 11 (low carbohydrate) in probands with both wild-type alleles, we observed decreases in BMI, weight, fat mass, systolic blood pressure, leptin levels, and insulin concentrations. In addition, with diet type 11, a decrease in diastolic blood pressure, total cholesterol, and triglyceride levels was detected. Secondary to diet type 1, a decrease in waist circumference and TNF-alpha was observed. Carriers of the T variant experienced decreases in BMI, weight, and fat mass on both diets, without statistical changes in biochemical parameters. In probands with both C alleles, both diets decreased insulin concentrations, blood pressure, and leptin concentrations. Weight reduction was similar with C and T alleles, independent of macronutrient distribution.